Physiological and pathophysiological roles of hypothalamic astrocytes in metabolism

Abstract

The role of glial cells, including astrocytes, in metabolic control has received increasing attention in recent years. Although the original interest in these macroglial cells was a result of astrogliosis being observed in the hypothalamus of diet‐induced obese subjects, studies have also focused on how they participate in the physiological control of appetite and energy expenditure. Astrocytes express receptors for numerous hormones, growth factors and neuropeptides. Some functions of astrocytes include transport of nutrients and hormones from the circulation to the brain, storage of glycogen, participation in glucose sensing, synaptic plasticity, uptake and metabolism of neurotransmitters, release of substances to modify neurotransmission, and cytokine production, amongst others. In the hypothalamus, these physiological glial functions impact on neuronal circuits that control systemic metabolism to modify their outputs. The initial response of astrocytes to poor dietary habits and obesity involves activation of neuroprotective mechanisms but, with chronic exposure to these situations, hypothalamic astrocytes participate in the development of some of the damaging secondary effects. The present review discusses not only some of the physiological functions of hypothalamic astrocytes in metabolism, but also their role in the secondary complications of obesity, such as insulin resistance and cardiovascular affectations.

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“…30 At the cellular level, leptin enhances glucose uptake through GLUT1. 31,32 In this study, a reduction in plasma leptin levels was observed. The reduction in leptin levels may have inhibited glucose uptake into cells and increased glycogenolysis.…”

Antisense therapy in a new rat model of Alexander disease reverses GFAP pathology, white matter deficits, and motor impairment

“…The copyright holder for this preprint this version posted January 31, 2021. ; https://doi.org/10.1101/2021.01.29.428244 doi: bioRxiv preprint balance (57)(58)(59)(60), and a detailed analysis of brainstem and hypothalamus will be essential in determining causes for failure to thrive and lethality in the model. Gfap-targeted ASO treatment leads to long lasting suppression of GFAP transcript and protein to below wild-type levels in both mouse and rat models of AxD.…”

“…Intractable vomiting is also observed in neuromyelitis optica (NMO) spectrum disorders, where the autoimmune response against the high levels of APQ4 in circumventricular organs can lead to area postrema syndrome (56), suggesting astrocyte dysfunction may be a common denominator for frequent emesis in both AxD and NMO. Several studies have also tied astrocyte function to hypothalamic regulation of food intake and energy balance (57)(58)(59)(60), and a detailed analysis of brainstem and hypothalamus will be essential in determining causes for failure to thrive and lethality in the model. Gfap-targeted ASO treatment leads to long lasting suppression of GFAP transcript and protein to below wild-type levels in both mouse and rat models of AxD.…”

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“…Therefore, astrocyte–neuron communication is key in the regulation of energetic signal transport and sensing by neurons. Indeed, studies have described the role of astrocytes in the detection of leptin, glucose, fatty acids, and amino acids and their involvement in the metabolic balance [ 218 , 219 , 220 , 221 , 222 , 223 ]. The role of astrocytes in glutamate recycling is also associated with the lactate supply to neurons for neurotransmitter action [ 222 ].…”